Table 1.

Summary of the Results from the In vivo Studies of p57KIP2 Aberrations in Several Types of Cancer

Type of CancerAlterations in p57KIP2References
Wilms' tumorNo mutations, frequent LOH in 11p15.5 (with a maternal bias) associated with decreased p57KIP2 mRNA; reactivation of the paternal p57KIP2 (LOI) in tumors with LOH; p57KIP2 expression varies58, 212-217
Soft tissue sarcomasNo mutations213
HepatoblastomaNo mutations; LOH with a maternal bias; increased mRNA expression of p57KIP2218
ALL, LMBALL: Downregulation of p57KIP2 (increased methylation of p57KIP2 promoter is partially associated with its decreased expression); AML: increased methylation of p57KIP2 promoter; LMB: no mutations, increased methylation of p57KIP2 promoterALL: 219-222; AML: 16; LMB: 223
AC and GBMAC: no mutations; GBM: decreased expression of p57KIP2126, 211
Oral squamous cell carcinomaNo mutations; LOH with no parental bias; increased mRNA expression in cases with LOI; decreased positive immunostaining of p57KIP2 protein224, 225
Laryngeal squamous cell carcinomaDecreased positive immunostaining of p57KIP2 protein226
Lung carcinomas (non-small cell lung carcinomas)No mutations; frequent LOH with a maternal allele bias; increased methylation of p57KIP2 promoter (and in a few cases upregulation of LIT1) related with decreased expression of p57KIP2; faint p57KIP2 positive immunostaining in tumor versus normal tissues; diminished p57KIP2 protein status associated with increased SKP259, 227, 228
Esophageal squamous carcinomap57KIP2-positive immunostaining at relatively high frequency in tumors246
Gastric carcinomaNo mutations; increased levels of miR-25, miR-221, and miR-222 (target p57KIP2)81, 229
PC and IPMNPC: p57KIP2-positive immunostaining decreases in cases with high biologic aggressiveness; IPMN: Decreased transcriptional and translational levels of p57KIP2 associated with promoter hypermethylation. A subset of specimens exhibited LIT1 hypomethylation because of deletion of the methylated LIT1 allele.PC: 231, 230; IPMN: 247
HC and EICHC: no mutations; downregulation of p57KIP2 related to loss of LIT1-ICR methylation; reduced positive immunostaining of p57KIP2 in cases with high biological aggressiveness; downregulation of p57KIP2 protein associated with upregulation of miR-221; EIC: Decreased expression of p57KIP2 in cases with biological aggressive phenotype;HC: 15, 80, 232-236; EIC: 237
Colorectal carcinomaDecreased positive immunostaining of p57KIP2 in colorectal carcinomas248
Bladder carcinomaNo mutations; diminished expression of p57KIP2 mRNA correlated in some cases with LOH; decreased expression of p57KIP2 positive immunostaining15, 238, 239, 249
Breast carcinomaNo mutations; Increased methylation of p57KIP2 promoter; decreased transcriptional levels and diminished positive immunostaining of p57KIP215, 88, 227, 240
Ovarian carcinomaIntense positive immunostaining of p57KIP2; decreased positive immunostaining in cases with high biological aggressive phenotype241, 242
Malignant adrenocortical tumorsReduced mRNA expression of p57KIP2243, 244
Thyroid carcinomasDecreased p57KIP2 positive immunostaining in cases with biological aggressive phenotype245

Abbreviations: AC, astrocytoma; ALL, acute lymphocytic leukemia; AML, acute myelogenous leukemia; EIC, extrahepatic bile duct carcinoma and intrahepatic cholangiocellular carcinoma; GBM, glioblastoma; HC, hepatocellular carcinoma; IPMN, intraductal papillary mucinous neoplasm; LMB, lymphoid malignancies of B-cell origin; LOH, loss of heterozygosity; LOI, loss of imprinting; PC, pancreatic carcinoma.